Subjects
Subjects were 137 consecutive patients who sought treatment for panic disorder at Nagoya City University Hospital Department of Psychiatry between June 2001 and March 2006. Of 137 patients, 95 subjects attended the group cognitive-behavioral therapy program.
At the start of the CBT program, all the patients met the following entry criteria:(a) principal Axis I diagnosis of panic disorder with or without agoraphobia according to the DSM-IV(Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria, as assessed by the Structured Clinical Interview for DSM-IV(SCID) [16]; (b) absence of a history of psychosis and current substance-use disorder; (c) highly motivated to undergo CBT. Patients with other comorbid anxiety disorders and/or major depressive disorders were admitted to the CBT program after the symptoms of these disorders had abated and they were able to participate in the program. At the start of the CBT program, of ninety-five patients, there are five with social phobia, 3 with obsessive-compulsive disorder, 3 with specific phobia, 5 with post-traumatic stress disorder and one with generalized anxiety disorder. As for depression at the start of the CBT program, there are three patients with present major depressive episode and five with dysthymic disorder.
Use of antidepressants to control their anxiety and/or depression was permitted throughout the CBT period. Because these drugs do not interfere with CBT treatments [17]. In case the patients were using benzodiazepines regularly or occasionally during the daytime to control their anxiety, we advised them to taper and stop usage or to switch to an antidepressant before starting the CBT program, since these drugs may interact negatively with exposure treatment [18]. Some patients reported that they had not been able to stop taking anxiolytic benzodiazepine by the start of the CBT program. Medications for symptoms other than anxiety were not restricted, so patients were allowed to use short-acting benzodiazepine hypnotic.
At the start of the CBT program, 56 patients used antidepressants, 19 patients used benzodiazepines regularly or occasionally.
The Ethics Committee of Nagoya City University Graduate School of Medical Sciences approved the study protocol and all subjects provided written informed consent after full explanation of the purposes and procedures of the study.
Treatment
CBT program used in this study was based on the CBT program developed by the Clinical Research Unit for Anxiety and Depression at the University of New South Wales, Sydney, Australia [19]. This treatment consists of five major components: (a) psycho-education concerning the nature, causes and maintenance of anxiety and panic; (b) breathing retraining; (c) cognitive restructuring; (d) graded situational exposure to reduce agoraphobic avoidance; (e) interoceptive exposure to reduce patients' fear of somatic sensations. Patients were assigned homework after each session.
One group consisted of three to four patients. Two trained therapists (psychiatrists or clinical psychologists with at least 2 years of clinical experience) conducted two-hour highly structured sessions once a week for ten weeks, using a detailed manual.
The senior psychiatrist, who had more than 15 years' experience as a clinician and had observed the PD-CBT program at St. Vincent's Hospital, trained the other therapists. With the aim of training, the junior psychiatrists or psychologists attended a series of CBT sessions as co-therapist, which facilitated mainly by the senior therapist. Then trained junior psychiatrist or psychologist began to lead a group CBT sessions assisted by another junior therapist. The senior psychiatrist supervised the other therapists at a CBT clinical conference held once a week.
Measures
Before enrolment into the CBT program, all participants received a semi-structured interview judging the anxiety and mood disorders section of the SCID and the Panic Disorder Severity Scale (PDSS). This interview was conducted by one of the clinicians carrying out the CBT program. Then at the start of the program, all patients completed five self-report questionnaires. To assess the intensity of catastrophic cognitions, patients were asked to fill out the Agoraphobic Cognitions Questionnaire (ACQ). To evaluate the clinical status and personality characteristics, patients completed the Work, Home and Leisure Activity Scales (WHLS), the Fear Questionnaire-agoraphobic subscale (FQ-ag), the Mobility Inventory for agoraphobia-alone subscale (MI-alone), and the NEO-Five Factor Inventory (NEO-FFI). The same sets of instruments except for the personality inventory were repeated at the end of the program. Three months after the end of the program, we mailed follow-up questionnaires including ACQ, FQ-ag, MI-alone, and WHLS. Details of these instruments are described below. Since we followed up by post mail, PDSS which is based on a semi-structured interview was not administered at 3-month follow-up.
Agoraphobic Cognitions Questionnaire (ACQ)
The ACQ is a 14-item self-report instrument to assess "fear of fear" or cognitions concerning catastrophic consequences of experiencing anxiety. Each item is rated on a five-point scale ranging from 1(thought never occurs) to 5(thought always occurs), according to the frequency with which this thought occurred when the client was anxious. Good reliability and validity have been shown for both the original and the Japanese versions of this questionnaire[20, 21].
Panic Disorder Severity Scale (PDSS)
The PDSS is a seven-item interview-based scale of panic disorder severity in which the clinician rates the severity of seven features of panic disorder on a scale rating from 0 (none) to 4 (extreme). The features that are rated include frequency of panic attack, distress during panic attack, anticipatory anxiety, agoraphobic fear/avoidance, interoceptive fear/avoidance, work impairment/distress, and social impairment/distress. Adequate inter-rater reliability and validity have been reported for both the original and the Japanese versions [22, 23].
The Work, Home and Leisure Activities Scale (WHLS)
The Work, Home and Leisure Activity Scales was designed to assess role functioning in the areas of work, home management, social leisure, and private leisure activities. Each item is rated on a nine-point scale ranging from 0 (not at all impaired) to 8 (very severely impaired). Satisfactory reliability and construct validity have been reported [24].
Fear Questionnaire-agoraphobia subscale (FQ-Ag)
The Fear Questionnaire-agoraphobia subscale is a self-report instrument for measuring the severity of agoraphobic avoidance of five typical situations for agoraphobia. Each situation is rated on a nine-point scale ranging from 0 (would not avoid it) to 8 (always avoid it) to show how much he/she would avoid each of the listed situations because of fear or other unpleasant feelings. Test-retest reliability and factor validity have been confirmed [25].
Mobility Inventory for agoraphobia-alone subscale (MI-alone)
The Mobility Inventory for agoraphobia is a self-report instrument for measuring the severity of agoraphobic avoidance. Patients are asked to rate on a five-point scale ranging from 1(never avoid) to 5(always avoid) to show how they feel about 31 places or situations that they may avoid because of anxiety or phobia, when they are alone. This instrument has been shown good reliability and construct validity [26, 27].
NEO-Five Factor Inventory (NEO-FFI)
The NEO-FFI is a 60-item self-reported inventory aimed to assess five personality factors of neuroticism, extraversion, conscientiousness, openness, and agreeableness [28].
Statistical analyses
To estimate the change of catastrophic cognition, we calculated the differences in ACQ total score across the treatment for each subject. Then we considered the standard error of measurement (http://www.w3.org/1998/Math/MathML1471-244X-7-70-i1SEM=σ1−γMathType-MTEF MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGacaGaaiaabeqaaeqabiWaaaGcbaGaee4uam1aaSbaaSqaaiabbweafjabb2eanbqabaGccqGH9aqpiiGacqWFdpWCdaGcaaqaaiabigdaXiabgkHiTiab=n7aNbWcbeaaaaa@35D2@: σ = standard deviation of normal population, γ = test-retest reliability coefficient). Since there was no available data revealing the stability of ACQ for a Japanese sample, we calculated the SEM for ACQ by using the data from Chambless et al.[20], and Chambless[29]. Based on the calculated SEM for ACQ total score (SEM = 2.41), we set the cut-off point at 3 as minimum change score. Each subject was classified as a "cognitive responding (CR)," or a "cognitively sensitized (CS)" based on their differences of ACQ total score across the treatment. The subject whose ACQ score at post-treatment was 3-point or more lower than pre-treatment ACQ score was classified as CR, and those whose post-treatment ACQ score was 3-point or more higher than pre-treatment ACQ score was classified as CS. Others who change the ACQ ranged from +2 to -2 across the treatment were considered as non-responder in cognition.
Following categorization of subjects, we compared the demographic data and the personality traits at the start of the CBT program among groups, using analysis of variance (ANOVA) for continuous variables and chi-squared test of independence for categorical variables. If the data distribution did not follow the normality assumption, Kruskal-Wallis Test was utilized.
We then focused on the differences between the CS and CR patients. First we compared these two groups in terms of their baseline clinical characteristics. The group mean values were compared using the independent Student t-test, as long as the variables were normally distributed within each group and the variation of scores in the two groups were not reliably different. If the data distribution did not follow the normality assumption, Mann-Whitney U test was utilized.
For the assessment of changes in symptom severity and functional impairment across treatment in both groups, Student's t-test for dependent samples was used. If the data distribution did not follow the normality assumption, Wilcoxon rank-sum test was utilized. The within-group treatment effect size (ES) was calculated by Cohen's d.
Further ANOVA for repeated measures with PDSS total score as the dependant variable was performed to evaluate whether the degree of improvement differed between the two groups.
To examine the course of symptomatic changes for the two groups, we conducted a 2(group: CS vs. CR) × 3(time: baseline vs. post-treatment vs. three-month follow-up) repeated measures ANOVA with FQ-ag score, MI-alone score and WHLS as the dependant variable, followed by the post-hoc Dunnett's test when appropriate. All data undergoing ANOVA were tested for assumption of sphericity with Mauchly's test. In cases the sphericity did not hold, we adjusted the degree of freedom for the F-test using the Greenhouse-Geisser epsilon.
Statistical analyses were performed using the SPSS program version 15.0. All the statistical tests were two-tailed, and results were considered significant when p < 0.05.